الفهرس 
CHILDHOOD INTERSTITIAL LUNG DISEASE (CHILD)Only 14 pages are availabe for public view
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Abstract
LPS-responsive beige-like anchor (LRBA) deficiency is an autosomal recessive primary immunodeficiency disorder and immune dysregulation syndrome caused by bi allelic mutations in the LRBA gene that have been linked to defective vesicle trafficking including transendocytosis and turnover of CTLA-4 in regulatory T cells (Treg). A decrease in LRBA protein function leads to the diminished expression of CTLA-4 on the surface of Treg cells. These mutations usually abrogate the protein expression of LRBA, leading to a broad spectrum of clinical phenotypes including enteropathy, autoimmune cytopenia, interstitial lung disease (ILD), normal immunoglobulin level or hypogammaglobulinemia, recurrent infections, bronchiectasis, and chronic lung diseases.
LRBA deficiency present with clinical, and radiological characteristics of interstitial lung disease.
Flow cytometry-based assay is a valuable and sensitive tool for investigating LRBA deficiency in peripheral blood cells after stimulation. Currently, the screening method for LRBA deficiency is based on gene sequencing approaches, but these are expensive, time-consuming, and are not performed in conventional diagnostic laboratories.
Some studies describing patients with LRBA deficiency focus on immunological and hematological characteristics. (Gámez-Díaz et al., 2016, Lopez-Herrera et al., 2012, Serwas et al., 2015, Shamriz et al., 2018). But, there are few studies focus on pulmonary manifestations in LRBA deficiency patients (Krone et al., 2021; Shamriz O et al., 2018).
The aim of our study was to assess expression of LRBA protien in patients with (ILD) and correlate (LRBA) deficiency to severity of (ILD) patients.
In our study, we report the respiratory manifestations, immunological, and radiological features of 6 newly diagnosed LRBA deficiency patients with ILD. Most of our LRBA deficiency patients presented with chronic cough, exercise intolerance, dyspnea, hypoxemia, crackles, digital clubbing, failure to thrive (FTT), organomegaly and recurrent sinopulmonary infections.
Most of our LRBA deficiency patients had normal immunoglobulins, normal CD19 count, low CD19+ CD27+ IgD- (class switched memory B cells), and high CD19+ IgD+ CD27- (naïve B cells).
The most important factors associated with LRBA deficiency abnormal pulmonary function tests (PFTs), IgM (mg/dl), IgA (mg/dl), CD19+ CD27+ IgD- (class switched memory Bcells), CD19+ IgD+ CD27- (Naïve B cells), Absolute CD 19 and FEV1/FVC ratio.
The features of HRCT chest presented in our LRBA deficient patients were ground glass pattern, thickened interlobular septa, reticulations, subpleural cyst, traction bronchiectasis, and tracheal retractions. Our LRBA deficient patients demonstrated restrictive pattern of PFTs.
Childhood interstitial lung disease (chILD) is a large and heterogeneous group of disorders characterized by diffuse lung parenchymal markings on chest imaging and clinical signs such as dyspnea and hypoxemia from functional impairment. Chest CT and pulmonary function testing were used to monitor for development and progression of pulmonary disease in LRBA deficiency patients.
Our study was done on 30 patients who are diagnosed ILD till age 18 years but the underlying cause is not known. There was no significant correlation between Immunoglobulins and Fan severity score of ILD, but there was significant negative correlation between IgG level and ATS grades of severity of this patients (the lower IgG level, the higher ATS grade of severity of ILD).
A timely and accurate diagnosis is essential to gauge treatment and improve prognosis. Current therapeutic options include anti-inflammatory and/or immunosuppressive drugs.
It is therefore imperative that patients with LRBA deficiency should be referred early to pulmonologists for thorough evaluation and management since delayed identification of subtle occult disease could result in increased morbidity and mortality.